Positron emission tomography (PET) is effective in diagnosing a variety of diseases including heart diseases and cancer. And in 2011, just under two million PET scans were performed in the US. These techniques generally involve administering an agent labeled with a radioisotope to a patient, followed by detecting γ-rays emitted directly or indirectly from the radiolabeled agent or so-called PET imaging probe.
[18F]2-fluoro-2-deoxy-D-glucose (FDG) is one imaging probe currently used for PET examination. FDG tends to be concentrated in areas where glucose metabolism is enhanced, thereby making it possible to detect tumors with accelerated glucose metabolism. While FDG remains the “gold standard” of PET imaging probes, its low specificity may produce suboptimal results in cancer imaging aimed at detecting small tumors and micro-metastases, especially in metabolically active tissues such as brain, liver, spleen, lung, and breast, such that it may be difficult to discern a signal given the noise.
Other PET imaging probes are being developed to avoid such shortcomings or are being sought for uses in other medical indications. As such, the development of new PET imaging agents and methodologies has received great interest. The attractiveness of the market for new PET imaging probes is evidenced by several novel PET probes currently in development. For example, 18F-FLT (SNMMI) is in a Phase 4 clinical trial for targeted breast cancer imaging, 18F-FCH (SNMMI) is in a Phase 0 clinical trial for prostate cancer staging, and 18F-FAC (Sofie Biosciences) is in a Phase 1 trial for cancer. In non-cancer indications, Flurpiridaz F-18 (Lantheus) is in a phase 3 clinical trial for myocardial perfusion imaging for the detection of coronary artery disease.
One challenge of developing PET imaging probes is the speed at which the probes can be prepared. The time it takes to prepare, purify, and isolate the probe following the labeling reaction with the 18F radioisotope is critical to there being sufficient radioactivity remaining in the probe to give sufficient signal to noise ratios during the PET scan. With the half-life of 18F at 110 minutes, reaction times longer than a few minutes waste the expensive radioactivity of 18F. As an example, the preparation of an imaging probe using an established 18F-labeling isotope called 4-[18F]fluorobenzoate-N-succinamide (SFB) takes 3 reaction steps and 80 minutes. Thus, what are needed are new 18F radiolabeling agents that can be used to rapidly radiolabel a wide variety of compounds. The compositions and methods disclosed herein address these and other needs.